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Identification of a dithiazoline inhibitor of Escherichia coli L,D-carboxypeptidase A. | LitMetric

Identification of a dithiazoline inhibitor of Escherichia coli L,D-carboxypeptidase A.

Antimicrob Agents Chemother

Johnson & Johnson Pharmaceutical Research & Development, L.L.C., 1000 Route 202, Raritan, New Jersey 08869, USA.

Published: November 2005

AI Article Synopsis

Article Abstract

The enzyme L,D-carboxypeptidase A is involved in the recycling of bacterial peptidoglycan and is essential in Escherichia coli during stationary phase. By high-throughput screening, we have identified a dithiazoline inhibitor of the enzyme with a 50% inhibitory concentration of 3 microM. The inhibitor appeared to cause lysis of E. coli during stationary phase, behavior that is similar to a previously described deletion mutant of L,D-carboxypeptidase A (M. F. Templin, A. Ursinus, and J.-V. Holtje, EMBO J. 18:4108-4117, 1999). As much as a one-log drop in CFU in stationary phase was observed upon treatment of E. coli with the inhibitor, and the amount of intracellular tetrapeptide substrate increased by approximately 33%, consistent with inhibition of the enzyme within bacterial cells. Stationary-phase targets such as L,D-carboxypeptidase A are largely underrepresented as targets of the antibiotic armamentarium but provide potential opportunities to interfere with bacterial growth and persistence.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1280138PMC
http://dx.doi.org/10.1128/AAC.49.11.4500-4507.2005DOI Listing

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